PROJECT SUMMARY/ABSTRACT This proposal aims to establish a foundation of patient-oriented research, which focuses on using neuroimaging to monitor treatment response among individuals with substance use disorders (SUD) participating in psychotherapy outcome research. The broad long-term objectives of this project are to determine how brain vulnerabilities, associated with addiction, vary as a function of resilience factors and targeted interventions. Insights from this proposal will contribute to the effort to improve treatment efforts for those in recovery from drug addiction. Mindfulness is characterized as present-centered nonjudgmental awareness, is a trainable quality of mind that can be measured, and is emerging as a construct highly salient to relapse prevention for those struggling with SUDs. Preliminary research has found that mindfulness and mindfulness training programs, among healthy individuals, associates with adaptive changes in the same brain regions that are disrupted in addiction. The primary aim of this proposal is to investigate the neural substrates of mindfulness and a mindfulness based intervention among those suffering with addiction to opiates (i.e., prescription pain relievers and heroin). The first aim of this proposal is to test the hypothesis that greater self-reported mindfulness will correspond to reduced neural reactivity in brain regions underscoring drug-cue motivational states (?craving?). To test this hypothesis, individuals with opiate use disorder (OUD) will complete an fMRI scan assessing brain activity during a drug-cue exposure probe. The second aim of this proposal is to determine how treatment, Mindfulness-Based Relapse Prevention (MBRP), designed to increase mindfulness and reduce drug use, associates with changes in brain function thought to underscore relapse vulnerability. This hypothesis will be tested by randomly assigning OUD participants to MBRP or Cognitive-Behavioral Therapy for Relapse Prevention (CBT) and assessing their brain function prior to and following treatment. Expected outcomes for this aim are that MBRP will associate with greater pre-post reductions in drug-cue related brain activity, relative to CBT. Finally, exploratory aims will test whether treatment effects (i.e., outcomes measuring drug use) are mediated by changes in brain activity. Integrating multi-modal assessment methods (i.e., neuroimaging, clinical and self-report measures, urinalysis) into a randomized clinical trial is highly innovative. Additionally, MBRP is an innovative and relatively new behavioral approach for SUDs that can provide unique insights into the role that mindfulness plays in adaptively modifying brain circuits underlying addiction. Findings from this research proposal will contribute to endeavor to improve addiction treatment efforts and will provide foundational support for pursuing additional R01 funding prior to the conclusion of this study. .